Journal article
Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population
Translational psychiatry, Vol.12(1), pp.247-247
06/13/2022
DOI: 10.1038/s41398-022-01982-2
PMCID: PMC9192633
PMID: 35697691
Abstract
The complexity of autism’s phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is undetermined if autistic symptom domain severity underlying this heterogeneity is heritable and pleiotropic with other psychiatric and behavior traits in the same manner as autism case-control status. In N = 6064 autistic children in the SPARK cohort, we investigated the common genetic properties of twelve subscales from three clinical autism instruments measuring autistic traits: the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), and the Developmental Coordination Disorder Questionnaire (DCDQ). Educational attainment polygenic scores (PGS) were significantly negatively correlated with eleven subscales, while ADHD and major depression PGS were positively correlated with ten and eight of the autism subscales, respectively. Loneliness and neuroticism PGS were also positively correlated with many subscales. Significant PGS by sex interactions were found—surprisingly, the autism case-control PGS was negatively correlated in females and had no strong correlation in males. SNP-heritability of the DCDQ subscales ranged from 0.04 to 0.08, RBS-R subscales ranged from 0.09 to 0.24, and SCQ subscales ranged from 0 to 0.12. GWAS in SPARK followed by estimation of polygenic scores (PGS) in the typically-developing ABCD cohort (N = 5285), revealed significant associations of RBS-R subscale PGS with autism-related behavioral traits, with several subscale PGS more strongly correlated than the autism case-control PGS. Overall, our analyses suggest that the clinical autism subscale traits show variability in SNP-heritability, PGS associations, and significant PGS by sex interactions, underscoring the heterogeneity in autistic traits at a genetic level. Furthermore, of the three instruments investigated, the RBS-R shows the greatest evidence of genetic signal in both (1) autistic samples (greater heritability) and (2) general population samples (strongest PGS associations).
Details
- Title: Subtitle
- Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population
- Creators
- Taylor R ThomasTanner KoomarLucas G CastenAshton J TenerEthan BahlJacob J Michaelson
- Resource Type
- Journal article
- Publication Details
- Translational psychiatry, Vol.12(1), pp.247-247
- DOI
- 10.1038/s41398-022-01982-2
- PMID
- 35697691
- PMCID
- PMC9192633
- NLM abbreviation
- Transl Psychiatry
- eISSN
- 2158-3188
- Grant note
- DOI: 10.13039/100000055, name: U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders, award: DC014489, DC014489, DC014489; DOI: 10.13039/100000025, name: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health, award: MH105527; DOI: 10.13039/100000893, name: Simons Foundation, award: 516716; DOI: 10.13039/100009633, name: U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development, award: P50HD103556; DOI: 10.13039/100000002, name: U.S. Department of Health & Human Services | National Institutes of Health, award: T32GM008629, T32GM008629; name: U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders; name: U.S. Department of Health & Human Services | National Institutes of Health; name: U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders
- Language
- English
- Date published
- 06/13/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984267260202771
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